Eliprodil
nmda modulator · intended neuroprotection after stroke/tbi class / nmda modulatorspec sheet6 rows
Eliprodil was one of the first NR2B-selective NMDA receptor antagonists to reach human trials, developed by the French pharmaceutical company Synthelabo in the late 1980s and 1990s as a neuroprotectant for stroke and traumatic brain injury. Instead of plugging the NMDA channel pore the way PCP-family blockers do, it binds at a separate polyamine site on the GluN2B subunit, a mechanism that produced much cleaner, less psychotomimetic behavior in animal models. It advanced into Phase III trials for TBI and stroke, but was discontinued in the late 1990s after trials were stopped over cardiac QT-interval prolongation and a lack of clear efficacy, joining aptiganel and several other NMDA blockers in the collapse of that entire drug class. Its real legacy is mechanistic: the NR2B-selective approach it pioneered was later picked up again by traxoprodil, rislenemdaz, and Novartis's MIJ821.
- fewer psychotomimetic effects than pore-blocking NMDA antagonists in preclinical models
- validated the NR2B polyamine site as a druggable target
- informed later, more selective NR2B compounds
- Eliprodil helped establish the entire NR2B-selective NMDA drug class that later produced traxoprodil, rislenemdaz, and MIJ821, even though it never made it to market itself.
- Its polyamine-site mechanism is still used as a reference point in PET radioligand research for imaging GluN2B receptors in living brains.
Mechanism
Non-competitive selective for GluN2B (NR2B)-containing receptors, binding at the polyamine modulatory site rather than the channel pore, intended to reduce excitotoxic injury after acute trauma with a cleaner side-effect profile than pore blockers.
Safetyrisks and cautions, not medical advice
The cardiac liability is the part worth knowing. Eliprodil blocks the rapid delayed rectifier potassium current, and in isolated dog and rabbit heart preparations it lengthened repolarisation; when the heart's repolarisation reserve was deliberately weakened first, two of six rabbit hearts went into torsade de pointes. That is laboratory work, not a clinical report. The Phase 3 stroke and head injury trials were stopped on a futility analysis for lack of effect, and the human cardiac dataset that would settle the question was never published.
History
Developed by Synthelabo (later Sanofi-Synthelabo) starting in the late 1980s; advanced into Phase III trials for TBI and acute stroke in the 1990s; discontinued after trials raised QT-prolongation concerns without a clear efficacy benefit.
Resources
This entry is here for reference.
Research
- 1.Eliprodil, a non-competitive, NR2B-selective NMDA antagonist, protects pyramidal neurons in hippocampal slices from hypoxic/ischemic damage
- 2.Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1A/NR2A and NR1A/NR2B receptors expressed in Xenopus oocytes
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
How is eliprodil different from PCP-type NMDA blockers?
It binds a separate polyamine site on the GluN2B subunit instead of plugging the channel pore directly, which gave it a cleaner behavioral profile in animal studies than pore blockers like MK-801 or PCP.
Is eliprodil related to traxoprodil?
They target the same GluN2B subunit through related mechanisms and came out of the same 1990s wave of NR2B-selective NMDA research, though they were developed by different companies (Synthelabo versus Pfizer).
Limitations of the evidence
- no clear efficacy benefit demonstrated in pivotal trials
- program discontinued before reaching approval
Notes and cautions
- QT interval prolongation